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Tetanus-diphtheria toxoid vaccination in adults

Tetanus-diphtheria toxoid vaccination in adults
Literature review current through: May 2024.
This topic last updated: Jun 07, 2023.

INTRODUCTION — Administration of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is routinely recommended in children, with a single booster dose of a vaccine containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) recommended for 11- to 12-year-olds, followed by tetanus toxoid and the reduced diphtheria toxoid in the form of Td or Tdap recommended at 10-year intervals throughout life (figure 1A-B). (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age".)

Despite these recommendations, immunity to tetanus and diphtheria continues to wane among adults in the United States. The magnitude of this effect was illustrated in a cross-sectional survey of individuals in the United States who were examined between 1988 and 1994 [1]. Only 47 percent of adults over the age of 20 had protective antibody to both diseases and only 63 percent of adults with immunity to tetanus also had protective antibody to diphtheria. In comparison, 91 percent of children from 6 to 11 years of age had protective antibody to both diseases. Immunity to pertussis also wanes among adolescents and adults. (See "Pertussis infection: Epidemiology, microbiology, and pathogenesis".)

The rationale and risk-benefit considerations for the administration of vaccination to prevent tetanus and diphtheria in adults will be reviewed here. Vaccination to prevent pertussis, immunizations in pregnant women, and the general principles behind adult immunization are discussed separately. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination' and "Standard immunizations for nonpregnant adults" and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Prevention'.)

EPIDEMIOLOGY OF DISEASE — The epidemiology of tetanus and diphtheria is discussed in detail elsewhere but will be briefly reviewed here. Both infections are completely preventable with safe and effective toxoid vaccines.

Tetanus — Because of near universal vaccination of children with tetanus toxoid, the incidence of tetanus in the United States and other resource-abundant countries has dropped dramatically and steadily since 1940. During the period between 2001 and 2016, the United States Centers for Disease Control and Prevention (CDC) reported that there were 462 cases of tetanus in the United States, including three neonatal cases [2]. Unpredictable acute injuries remain the major cause of tetanus in the United States. Adults age 65 years and older are at highest risk for both tetanus and tetanus-related death [3]. Despite the low rate of clinical disease, many adults are inadequately vaccinated against tetanus. (See 'Routine adult immunization' below.)

In contrast to resource-abundant nations, approximately 1,000,000 cases of tetanus are estimated to occur in resource-limited countries each year. (See "Tetanus", section on 'Epidemiology'.)

Diphtheria — Approximately 20 to 60 percent of adults become susceptible to diphtheria because of waning vaccine-induced immunity and failure to receive recommended booster immunization. (See 'Routine adult immunization' below.)

Despite the frequent lack of immunity, there is still a low rate of clinical disease because immunization of the population has minimized the transmission of toxigenic strains. Only 13 cases of respiratory diphtheria were reported to the CDC from 1996 to 2016 (zero to five cases in any given year) [2]. However, unvaccinated or inadequately vaccinated travelers to endemic areas are at risk for acquiring this infection. (See "Epidemiology and pathophysiology of diphtheria".)

For reasons that are not well understood, pockets of diphtheria are reappearing, primarily in resource-limited countries. The epidemics have involved nonimmunized or poorly immunized adults in addition to children.

INDICATIONS FOR TD OR TDAP VACCINATION IN ADULTS

Routine adult immunization — In the United States, a diphtheria-tetanus toxoid (Td) or diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine (Tdap; Adacel or Boostrix) vaccine 0.5 mL intramuscularly (IM) is recommended every 10 years for all adults with complete prior immunization against tetanus and diphtheria [2,4,5]. At least one of those doses should be with Tdap in adults aged 19 years and older who had not received Tdap previously. When indicated, Tdap should be administered regardless of the interval since the last dose of Td. Subsequently, booster doses with either Td or Tdap can be resumed 10 years later.

Adults who have not been previously vaccinated against tetanus and diphtheria should receive a series of three vaccines (at least one Tdap; the other two can be either Td or Tdap vaccines) [2]. The preferred schedule is a Tdap vaccine dose followed by a Td or Tdap vaccine dose four weeks later and another Td or Tdap vaccine dose 6 to 12 months later.

The following figures summarize the Advisory Committee on Immunization Practices (ACIP) recommendations for immunization of adults without and with comorbidities, respectively (figure 2 and figure 3) [4]. Previously, ACIP only recommended a single Tdap dose, with the rest of tetanus and diphtheria vaccination to be completed with Td; in 2020, it recommended that either Tdap or Td could be used for additional catch-up or booster doses following the Tdap dose since Tdap has a reassuring safety profile and allows providers more flexibility in choice of vaccine. The CDC also provides guidance regarding the choice of vaccine in the setting of a shortage. The use of Tdap for prevention of pertussis is discussed in detail separately. (See "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Vaccination'.)

The rationale for universal vaccination against tetanus and diphtheria every 10 years is waning immunity. In a serologic survey in the United States between 1988 and 1994, fully protective levels of anti-tetanus and anti-diphtheria antibodies were detected in 91 percent of individuals aged 6 to 11 years but in only 47 percent of individuals 20 years or older [1]. Not surprisingly, protective antibody levels were more likely in adults with a history of military service, higher levels of education, higher incomes, and medical insurance [6,7].

Similar findings were noted with diphtheria immunity in a 1995 study of 1000 United Kingdom-born blood donors in North London: 38 percent were susceptible to diphtheria (serum diphtheria antitoxin concentration below 0.01 international units/mL), 31 percent had basic protection, and 31 percent were fully protected [8].

Older adults, in particular, are less likely to have detectable tetanus or pertussis antibodies as a result of either never receiving a primary diphtheria, pertussis, and tetanus (DPT) vaccination or waning immunity in those who never received subsequent tetanus toxoid booster doses [3]. In the United States serologic survey discussed above, only 31 percent of individuals older than 70 years had protective tetanus and diphtheria antibodies [1]. In a subsequent study from the mid-1990s of adults in the United States, increasing age was associated with a lower likelihood of tetanus toxoid receipt in the prior 10 years: 65 percent between the ages of 18 and 49 years, 54 percent between the ages of 50 and 64 years, and 40 percent ≥65 years of age [7].

Immunization during pregnancy — In the United States, the ACIP recommends that all pregnant women receive vaccination against pertussis with Tdap during each pregnancy [9]. Detailed recommendations are presented separately. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

Immunization for patients with injuries — Regardless of prior tetanus and diphtheria immunization, Tdap immunization should be reviewed when anyone presents with an acute injury or wound and prophylaxis (ie, tetanus toxoid-containing vaccine with or without human tetanus immune globulin) should be administered as indicated (table 1) [4].

Most patients who develop tetanus are not completely vaccinated and do not receive adequate wound prophylaxis, even when they present for medical care [3]. Incomplete vaccination is more likely in the following groups:

Injection drug users

Immigrants

Rural populations

Older adults

For patients who have received fewer than three doses or an unknown number of doses of a tetanus toxoid-containing vaccine, tetanus immunization should be administered (table 1) [4]. The preferred vaccine preparation depends upon the age and vaccination history of the patient. For patients with clean minor wounds who have received three or more doses of a tetanus toxoid-containing vaccine, another dose should be given only if the last dose was given 10 or more years ago. For patients with wounds that are more severe than a clean and minor wound (such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; wounds resulting from missiles, crushing, burns, or frostbite) who have received three or more doses of a tetanus toxoid-containing vaccine, another dose should be given only if the last dose was given five or more years ago. The vaccine series should be continued through completion as necessary. If there is any doubt about whether or not an adult received the primary series, three doses of Td or Tdap (with Tdap given for at least one of the doses) should be administered; the first dose and second dose should be separated by four weeks and the third dose should be given 6 to 12 months later (figure 2 and figure 3).

Since inadequate protection against diphtheria and tetanus often occur together [1], Td or Tdap is the preferred vaccine, not tetanus toxoid alone. (See 'Routine adult immunization' above and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Prevention'.)

In addition to tetanus immunization, human tetanus immune globulin (250 units intramuscularly [IM]) is indicated in individuals who have sustained a wound that is more severe than a clean and minor wound (eg, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; wounds resulting from missiles, crushing, burns, or frostbite) and who have either received fewer than three doses of tetanus toxoid previously or in whom the number of previous doses is unknown. Tetanus immune globulin is also recommended for HIV-infected patients and severely immunocompromised patients with concerning wounds, regardless of their tetanus immunization history [2].

Appropriate tetanus prophylaxis should be administered as soon as possible following a wound but should be given even to patients who present late for medical attention. This is because the incubation period is quite variable; the incubation period of tetanus is approximately 8 days but ranges from 3 to 21 days [10]. (See "Tetanus", section on 'Incubation period'.)

Adverse effects — Severe systemic reactions, such as anaphylaxis, generalized urticaria, angioedema, and neurologic complications, have been reported following Td administration, but a causal relationship between the neurologic complications and vaccine administration have not been established. Patients who develop an arthus-like reaction tend to have high serum antitoxin levels and should be instructed to avoid booster doses more often than every 10 years. (See "Allergic reactions to vaccines".)

CONTRAINDICATIONS AND PRECAUTIONS — Contraindications and precautions to diphtheria-tetanus toxoid (DT and Td) and diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine (DTaP and Tdap) are summarized in the drug information topics within UpToDate.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in adults" and "Society guideline links: Diphtheria, tetanus, and pertussis vaccination".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Tetanus (The Basics)" and "Patient education: Vaccines for adults (The Basics)" and "Patient education: What you should know about vaccines (The Basics)" and "Patient education: Tdap vaccine (The Basics)")

Beyond the Basics topic (see "Patient education: Vaccines for adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Routine tetanus immunization – Administration of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine is routinely recommended in children, with a single booster dose of a vaccine containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) recommended for 11- to 12-year-olds, followed by tetanus toxoid and the reduced diphtheria toxoid in the form of Td or Tdap recommended at 10-year intervals throughout life (figure 1A and figure 1B).

Despite these recommendations, immunity to tetanus and diphtheria continues to wane among adults in the United States. Thus, in the United States, a diphtheria-tetanus toxoid (Td) or diphtheria toxoid-tetanus toxoid-acellular pertussis vaccine (Tdap; Adacel or Boostrix) vaccine 0.5 mL intramuscularly (IM) is recommended every 10 years for all adults with complete prior immunization against tetanus and diphtheria. (See 'Routine adult immunization' above.)

Recommendations on the use of Tdap in adults (including during pregnancy) for the prevention of pertussis are discussed elsewhere. (See "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Vaccination' and "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)

Tetanus prophylaxis in patients with an injury

Tetanus immunization – Regardless of prior tetanus and diphtheria immunization, Td immunization should be reviewed when anyone presents with an acute injury or wound. The approach to tetanus immunization is described in the table (table 1). This can also provide an opportunity to administer Tdap if it is available and if it is not clear whether the patient previously received Tdap.

Use of tetanus immunoglobulin – Human tetanus immune globulin should be administered in addition to tetanus immunization to individuals who have sustained a wound that is more severe than a clean and minor wound (eg, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; wounds resulting from missiles, crushing, burns, or frostbite) and who have either received fewer than three doses of tetanus toxoid previously or in whom the number of previous doses is unknown. (See 'Immunization for patients with injuries' above.)

Need for catch-up immunization – If there is any doubt about whether or not an adult received the primary series, three doses of tetanus and diphtheria toxoid-containing vaccine should be administered for catch-up vaccination; this applies to routine tetanus immunization as well as prophylaxis after an injury.

At least one of these doses should be with Tdap. The preferred schedule is a Tdap vaccine dose followed by a Td or Tdap vaccine dose four weeks later and another Td or Tdap vaccine dose 6 to 12 months later (table 1). (See 'Immunization for patients with injuries' above.)

  1. McQuillan GM, Kruszon-Moran D, Deforest A, et al. Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med 2002; 136:660.
  2. Liang JL, Tiwari T, Moro P, et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2018; 67:1.
  3. Centers for Disease Control and Prevention (CDC). Tetanus surveillance --- United States, 2001-2008. MMWR Morb Mortal Wkly Rep 2011; 60:365.
  4. Kim DK, Hunter P, Advisory Committee on Immunization Practices. Recommended Adult Immunization Schedule, United States, 2019. Ann Intern Med 2019; 170:182.
  5. Havers FP, Moro PL, Hunter P, et al. Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccines: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2019. MMWR Morb Mortal Wkly Rep 2020; 69:77.
  6. Gergen PJ, McQuillan GM, Kiely M, et al. A population-based serologic survey of immunity to tetanus in the United States. N Engl J Med 1995; 332:761.
  7. Singleton JA, Greby SM, Wooten KG, et al. Influenza, pneumococcal, and tetanus toxoid vaccination of adults --- United States, 1993--1997. MMWR Surveill Summ 2000; 49:39.
  8. Maple PA, Efstratiou A, George RC, et al. Diphtheria immunity in UK blood donors. Lancet 1995; 345:963.
  9. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep 2013; 62:131.
  10. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Tetanus. https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html (Accessed on September 06, 2017).
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